Viruses having a lipid envelope or coat are important human and animal pathogens, Examples of conditions associated with such viruses include HIV, Hepatitis, Ross River and Herpes. The Herpes viruses cause both primary and secondary infections that range from trivial mucosal ulcers to life threatening disorders in immuno-compromised patients. The Herpes group includes HSV-1, HSV-2, Herpes Zoster (chicken pox/shingles), HCMV (human cytomegalovirus), Epstein Barr Virus (EBV), Herpes 6, 7 (Roseola, post transplant infections) and Herpes 8 (associated with Kaposi sarcoma).
Persons infected with a Herpes type virus are typically subjected to cycles of outbreaks where symptoms are experienced and asymptomatic latent periods. During the latent periods, the virus resides in the ganglia where it is inactive and the patient is asymptomatic. However, although asymptomatic, a patient may still be able to infect others. This is known as viral shedding. Reoccurrence of symptoms can occur when the virus is reactivated. Reactivation can be triggered by many different events and is particularly problematic in immunocompromised patients.
The conventional treatment of these infections is with drugs such as acyclovir (ACV) that target the viral DNA polymerase.
There are two generally recognized types of Herpes drug therapy. The first is often referred to as “Outbreak therapy” in which a patient begins drug therapy at the first indication of an outbreak. Following cessation of symptoms, drug therapy is discontinued. A disadvantage of such therapy is that recurrences of infection are not controlled. An alternative therapy is known as “Suppressive therapy” which involves long term doses of maintenance anti-Herpes drug levels. However, whilst the currently available drugs are undoubtedly efficient, they may possibly have side effects, and long-term use has led to the development of resistant viral strains. Such strains now comprise 5% of all HSV infections in immunocompromised patients. There is also patient concern with ongoing drug intake, together with the associated high cost of these drugs.
Subsequently, finding non-toxic alternatives and/or adjuncts to these drugs is extremely important for treatment of patients and also potentially as a prophylactic.
There are a plethora of classes of chemical compounds with putative antiviral effects. One such class is known broadly as the sulfated polysaccharides. The sulfated polysaccharides are an extremely large class of compounds and include sulfated homopolysaccharides, sulfated homooligosaccharides, sulfated heteropolysaccharides, sulfated heteroologosaccharides, sulfoglycolipds, carrageenans and fucoidans. Fucoidans are long branched chains of sugars found in marine algae and echinoderms which include a substantial amount of fucose.
Although encompassed by a single term, the chemical and physical properties of the respective fucoidans vary considerably between species. Such properties include degree of sulfation, molecular weight, degree of branching, linkage positions and fucose content, For example fucoidan from Fucus vesiculosis contains about 90% fucose, while fucoidan from Undaria contains about 50% fucose and about 50% galactose and is known as galactofucan or fucogalactan sulfate. The fucoldans from echinoderms are substantially linear whereas those from alga are highly branched.
Characterization of the fucoids has been severely inhibited by their complexity and the random nature and heterogeneity of the sugar backbone.
Sulfated polysaccharides are believed to be of potential therapeutic importance because they can mimic sugar rich molecules known as glycosaminoglyeans (GAGs). Examples of GAGs which are important in mammalian physiology are heparin sulfate, dermatan sulfate and chondroitin sulfate. Heparin, for example, is a critical regulatory factor of the blood clotting cascade.
Heparin sulfate receptors on cell surfaces are important in many physiological and pathological processes. They are key entry points for viral entry into some cells and are also necessary for leukocyte movement into tissues and for metastasis. It has been postulated that sulfated polysaccharides such as algal fucoidans may compete for binding sites normally occupied by GAGs and thus inhibit these processes.
Many studies have been conducted with a view to investigating the in vitro anti-viral activity of various sulfated polysaccharides. Studies have generally concentrated on synthetic dextran sulfates, pentosan sulfates, clinically used heparins, and seaweed derived carageenans. One review reports that sulfated homopolysaccharides are more potent than sulfated heteropolysaccharides. (Schaffer DJ et al., 2000 Ecotoxicology and Environmental Safety 45:208–227, Witvrouw M et al 1997 Gen Pharmacol 29:497–511). Another review expresses concern about the viability of sulfated polysaccharides as in vivo anti-viral agents in view of believed low bloavailability (Luscher-Mattli M, 2000 Antiviral Chemistry and Chemotherapy 11(4):249–259). One study which investigated the exploitation of cell-surface GAG's by HIV found that cell-surface heparin sulfate facilitates HIV entry into some cell lines but not primary lymphocytes. The authors expressed caution about extrapolating in vitro results obtained from immortalized cell lines. (Ibrahin J, Griffin P, Coombe D R, Rider C C and James W. Virus Res. 1999 Apr;60(2); 159–69).
Despite the recognized need for alternative anti-viral therapies and the interest in sulfated polysaccharides, to date the present inventors are unaware of any clinical studies on the potential anti-viral effects of sulfated polysaccharides.
Advantageously, it has been discovered that an Undaria extract containing galactofucan sulfate is useful in the treatment and/or prevention of conditions associated with viral infections.